Each year, arthritis results in 44 million outpatient visits, 992100 hospitalizations, and 700000 knee replacement procedures (www.cdc.gov/arthritis). The need for knee replacement is rapidly increasing, with 3.48 million expected procedures by 2030. However, artificial implants are associated with potential complications, such as periprosthetic fractures, loosening, and metal sensitivity. Even in the absence of complications, the lifetime of an artificial prosthesis is limited to approximately 10 years as the implant wears out.
Cell transplants, particularly stem cell-scaffold nanocomposites, could overcome these problems by providing long-term biologic restoration of joint defects. Bone marrow-derived mesenchymal stem cells (MSCs) have been established as a promising source for stem cell-mediated joint repair in a clinical setting. MSCs can be obtained with a bone marrow aspirate, are expanded in vitro, and can differentiate into all joint components. However, interactions between transplanted MSCs and the patient's host environment are still poorly understood.
To monitor successful engraftment and recognize complications such as graft failure or tumor formation, MSC therapies require tracking of the transplanted stem cells. In the past, stem cell tracking has been achieved on the basis of the concept of ex vivo contrast agent labeling. This approach requires multiple ex vivo manipulations of stem cells between their harvest and transplantation.
Clinical translation of ex vivo-labeling procedures is complicated from a regulatory point of view as these manipulations greatly enhance the risk of cell sample contamination, alterations in stem cell biology, or in vivo side effects from added transfection agents. Most transfection agents (LIPOFECTAMINE 2000 [Invitrogen, Carlsbad, Calif.] or poly-L-lysine [Sigma-P4707; Sigma-Aldrich, St Louis, Mo.]) are not U.S. Food and Drug Administration (FDA) approved. In addition, some ultra-small super-paramagnetic iron oxide-transfection agent combinations have induced cytotoxic effects or altered the stem cell biology.
Accordingly, the art is in need of more immediately clinically applicable methods for stem cell labeling, which would not require ex vivo manipulations of harvested cells and which would eliminate the need for transfection agents, that then could be used to track transplanted MSCs. The present invention addresses this need.